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Fig. 3 | Molecular Neurodegeneration

Fig. 3

From: Tau mutant A152T, a risk factor for FTD/PSP, induces neuronal dysfunction and reduced lifespan independently of aggregation in a C. elegans Tauopathy model

Fig. 3

Mutant TauAT induces morphological changes in mechanosensory neurons early in the adulthood and reduces life-span. a Cartoon depicting a normal healthy neuron and a neuron showing morphological changes associated with aging like sprouting, non-specific branching and bending. b Mutant TauAT worms show neuronal abnormalities reminiscent of aging neurons. Pmec-4::gfp reporter that expresses GFP in mechanosensory neurons, was crossed into tau-transgenic worms and neurons visualized for morphological abnormalities at the days indicated. Note the soma outgrowth (yellow arrowhead) and bending of neuronal process (white arrow) in TauAT-lo at day 1. At this age, Tauwt (both -lo and -hi) show normal morphology and do not differ from non-tg. Only the incidence of an infrequent posterior extension (white arrow heads) increases in the Tauwt worms (to 30 % compared with 10 % in non-tg at day 1), whereas in TauAT-lo this posterior extension occurs in almost 100 % of the animals. c The severity of the phenotype increases with age. Soma outgrowths visible in TauAT-lo animals at day 1 grow and undergo further branching with age (yellow double arrowhead). The volume marker GFP accumulates in beaded structures in the posterior extension in TauAT-lo worms and small outgrowths emanate from posterior extension (white double arrowhead). These beaded structures could represent starting points of new branches, and were previously shown to be associated with mitochondria [24]. d Quantification of animals with gross non-specific neuronal abnormalities (bends and branches) at two time points, day 1 and day 3. Error bars denote mean ± SEM, n ≥ 20. **P ≤ 0.01, ***P ≤ 0.001. Paired t-test with unequal variance was used for comparison. e Representative survival curves of tau-transgenic animals, non-tg serves as control. Mantel-Cox log-rank test was performed to determine the statistical significance for the worm life-span. (for P-values see Table 2)

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